Endoscopic Resection of Gastrointestinal Neuroendocrine Tumors: Long-Term Outcomes and Comparison of Endoscopic Techniques.

Introduction: Gastrointestinal neuroendocrine tumors (GI-NETs) are being more frequently diagnosed and treated by endoscopic resection (ER) techniques. However, comparison studies of the different ER techniques or long-term outcomes are rarely reported. Methods: This was a single-center retrospective study analyzing short and long-term outcomes after ER of gastric, duodenum, and rectal GI-NETs. Comparison between standard EMR (sEMR), EMR with a cap (EMRc), and endoscopic submucosal dissection (ESD) was made. Results: Fifty-three patients with GI-NET (25 gastric, 15 duodenal, and 13 rectal; sEMR = 21; EMRc = 19; ESD = 13) were included in the analysis. Median tumor size was 11 mm (range 4-20), significantly larger in the ESD and EMRc groups compared to the sEMR group (p < 0.05). Complete ER was possible in all cases with 68% histological complete resection (no difference between the groups). Complication rate was significantly higher in the EMRc group (EMRc 32%, ESD 8%, and EMRs 0%, p = 0.01). Local recurrence occurred in only one patient, and systemic recurrence in 6%, with size ≥ 12 mm being a risk factor for systemic recurrence (p = 0.05). Specific disease-free survival after ER was 98%. Conclusion: ER is a safe and highly effective treatment particularly for less than 12 mm luminal GI-NETs. EMRc is associated with a high complication rate and should be avoided. sEMR is an easy and safe technique that is associated with long-term curability, and it is probably the best therapeutic option for most luminal GI-NETs. ESD appears to be the best option for lesions that cannot be resected en bloc with sEMR. Multicenter, prospective randomized trials should confirm these results.

Introdução: Os tumores neuroendócrinos gastrointestinais (GI-NET) são frequentemente diagnosticados e tratados por técnicas de resseção endoscópica (ER). Contudo, estudos comparativos das diferentes técnicas de ER ou resultados a longo prazo são raramente descritos. Métodos: Estudo unicêntrico retrospectivo que analisa resultados a curto e longo prazo após ER de NETs gástricos, duodenais e retais. Realizou-se uma análise comparativa entre as técnicas de mucosectomia convencional (sEMR), mucosectomia com cap (EMRc) e disseção endoscópica da submucosa (ESD). Resultados: Foram incluídos 53 doentes com GI-NET (25 gástricos, 15 duodenais e 13 rectais; sEMR=21; EMRc=19; ESD=13). A mediana do tamanho da lesão foi 11 mm (âmbito 4-20), sendo significativamente maiores nos grupos ESD e EMRc quando comparado com sEMR (p < 0.05). A ER completa foi possível em todos os casos com taxa de resseção histológica completa de 68% (sem diferença entre os grupos). A taxa de complicações foi significativamente superior no grupo EMRc (EMRc 32%, ESD 8% e EMRs 0%, p = 0.01). Recorrência local apenas ocorreu em 1 doente e recorrência sistémica em 6%, com o tamanho da lesão ≥ 12mm a ser um factor de risco para recorrência sistémica (p = 0.05). Sobrevida específica de doença após ER de 98%. Conclusão: ER é segura e altamente eficaz para o tratamento de GI-NETs principalmente com tamanho inferior a 12 mm. EMRc está associada a uma taxa de complicações elevada e deve ser evitada. sEMR é uma técnica segura e eficaz que se associa a curabilidade a longo prazo, sendo provavelmente a melhor opção terapêutica para a maioria dos GI-NETs luminais. ESD parece ser a melhor opção para as lesões que não podem ser removidas em bloco pela técnica de sEMR. Estudos randomizados, prospectivos e multicêntricos devem confirmar estes resultados.

Attenuation of toll-like receptor 2-mediated innate immune response in patients with alcoholic chronic liver disease.

BACKGROUND: Alcoholic chronic liver disease (ACLD) is a common form of acquired immunodeficiency. AIM: To evaluate ex vivo toll-like receptor (TLR) 2 and TLR4 innate immune response in stable ACLD. METHODS: Blood was collected from 26 males with stable ACLD and from 17 controls. Serum was used for lipopolysaccharide (LPS), sCD14, LPS-binding protein (LBP), tumour necrosis factor-alpha (TNF-alpha) and interleukin 10 (IL-10) quantification. Peripheral blood monocytes (PBM) protein expression of TLR2 and TLR4 was determined by flow cytometry. Primary cultures of anti-CD11b positive selected PBM were stimulated with the TLR2/TLR6 ligand zymosan (Zym), with TLR2/TLR1 ligand lipopeptide (Lp) and with TLR4 ligand LPS. PBM TLR1, TLR2, TLR4, TLR6, MD2, CD14, TNF-alpha and IL-10 gene expression was evaluated by reverse transcription-polymerase chain reaction. RESULTS: Stable ACLD patients showed increased circulating LPS (+22.5+/-4.1%), LBP (+60.6+/-12.2%) and sCD14 (+23.5+/-4.6%), with no differences in TNF-alpha and IL-10. Zym and Lp, but not LPS, induced TNF-alpha production by monocytes was blunted in ACLD (-66+/-20.4% Zym; -40.1+/-13.5% Lp; P<0.05). Basal TNF-alpha mRNA expression was decreased in PBM from ACLD patients (-50.1+/-21.0%; P<0.05), with no significant differences in the other studied genes. Results were similar in Child-Pugh A and B/C patients. CONCLUSIONS: Patients with stable ACLD show an attenuation of TLR2-mediated innate immune response in PBM, which may represent an important mechanism for acquired immunodeficiency. This was neither related with decreased TLR2 or its co-receptors expression nor with impaired TLR4 activation, being already present in the early stages of disease.

Covered Metal Stent after Dysfunction of Uncovered Stents for Palliation of Gastrointestinal Malignant Obstruction.

BACKGROUND: Self-expanding metal stents (SEMS) have been used for the palliative treatment of malignant gastrointestinal tract obstruction. However, restenosis or incomplete expansion of a first stent is a frequent complication, and the effectiveness of reintervention with placement of a second stent is still controversial. OBJECTIVE: To evaluate the clinical outcomes of covered SEMS (cSEMS) placement after dysfunction of uncovered SEMS (uSEMS) by the stent-in-stent technique. PATIENTS AND METHODS: We retrospectively studied a consecutive series of patients receiving palliative treatment for malignant gastrointestinal obstruction with cSEMS placement after uSEMS dysfunction in a tertiary center from January 2013 to August 2018. Technical and clinical success, time of patency, and adverse events were analyzed. RESULTS: Twelve patients were included; their mean age was 60 ± 9 years. Eleven patients had gastric outlet obstruction, and 1 patient had compression of the transverse colon due to gastric neoplasia. In 5 cases, there was absence of early clinical success with uSEMS and stent dysfunction in 7 cases (median patency time: 81 days). There was 100% technical success and 91.7% clinical success after cSEMS placement. There were no adverse events nor need for reintervention. The median patency time after placement of both stents was 163 days (vs. 71 days with the initial stent). CONCLUSION: cSEMS placement after uSEMS dysfunction is technically feasible and a clinically effective treatment for patients with recurrent malignant gastrointestinal obstruction, with good stent patency in the medium/long term. This approach seems to be safe and without increase in adverse effects.

INTRODUÇÃO: As próteses metálicas autoexpansíveis (PMAE) têm sido utilizadas para a paliação de obstruções malignas do trato gastrointestinal. No entanto, a reestenose ou a expansão incompleta das próteses é uma complicação frequente e a eficácia de uma reintervenção com a colocação de uma segunda prótese é ainda controversa. OBJETIVO: Avaliar os resultados clínicos da colocação de PMAE cobertas (cPMAE) após disfunção de PMAE não-cobertas (ncPMAE) pela técnica de stent-in-stent. MÉTODOS: Estudo retrospetivo, incluindo uma série consecutiva de doentes que colocaram cPMAE após disfunção ncPMAE para paliação de obstrução gastrointestinal maligna, num centro terciário, de janeiro/2013 a agosto/2018. Foram avaliados o sucesso técnico e clínico, o tempo de patência e os eventos adversos. RESULTADOS: Foram incluídos 12 doentes, com uma idade média de 60 ± 9 anos. Onze doentes apresentavam obstrução do trato de saída gástrico e um doente compressão extrínseca do cólon transverso por neoplasia gástrica. Em 5 doentes verificou-se ausência de sucesso clínico precoce com ncPMAE e, em 7 casos, disfunção da prótese (tempo mediano de patência de 81 dias). Houve 100% de sucesso técnico e 91,7% de sucesso clínico após a colocação do cPMAE. Não se registaram eventos adversos ou necessidade de reintervenção. O tempo médio de patência após a colocação de ambas as próteses foi de 163 dias (vs. 71 com prótese inicial). CONCLUSÃO: A colocação de cPMAE após disfunção de ncPMAE é tecnicamente viável e representa um tratamento eficaz em doentes com obstrução gastrointestinal maligna recorrente, com boa patência da prótese a médio/longo prazo. Esta abordagem parece ser segura, sem aumento de eventos adversos.